Candidate: Kristine B. Patterson, MD, Assistant Professor of Medicine at the University of North Carolina (UNC) has begun formal clinical trial training through the NIH-sponsored Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program. Career Goals: My vision is to be a clinician scientist with expertise in clinical pharmacology who is independently conducting clinical trials in HIV-infected women. Career Development Plans: Dr. Patterson will obtain formal training in clinical pharmacology and enhance her basic knowledge of quantitative methods and clinical trials research conduct through the Master of Science in Clinical Science graduate program. She will obtain hands on training while performing the clinical studies and analyses outlined in the research plan. Immediate Objective: To acquire expertise in clinical pharmacology and the design, implementation, data collection, and analysis of clinical trials. Long-term Objective: To use these skills to further the pharmacologic interventions available to HIV-infected women to increase treatment responses and to decrease infectiousness. Specific Aims: 1) To measure and compare steady state blood plasma pharmacokinetics of antiretroviral therapies in post- and pre-menopausal HIV- infected women. 2) To longitudinally quantify and compare genital tract antiretroviral drug exposure in post- and pre-menopausal HIV-infected women. 3) To determine and compare sexual HIV infectivity in post- and pre-menopausal HIV-infected women by measuring HIV RNA dynamics in blood plasma and genital tract secretions before and after the initiation of highly active antiretroviral therapy. Research Methods: First- dose, steady-state and longitudinal pharmacokinetics of the most commonly prescribed antiretroviral agents will be assessed in the systemic and genital tract compartments in a cohort of post- and pre-menopausal HIV-infected women. Concurrent blood plasma and genital secretions HIV RNA will be measured. Systemic and genital tract virologic responses will be correlated with antiretroviral concentrations and with each other. Environment: This study will take place at UNC's General Clinical Research Center. Subjects will be recruited from the UNC HIV Clinic and UNC's associated satellite clinics. The UNC Schools of Medicine, Pharmacy and Public Health will provide a rich learning environment for Dr. Patterson's training. Mentorship: The two primary mentors have expertise in HIV (J. Eron) and HIV pharmacology (A. Kashuba) and will oversee a team of productive, successful investigators that boasts strong foundations in the disciplines to be learned by Dr. Patterson, including gynecological (K. Nanda) and hormonal (J. Rubin) changes associated with aging, immunology (D. Margolis), genital tract virology (S. Fiscus) and biostatistics (C. Moore). Relevance: The knowledge gained through this training program and from this study will be used to design studies that modulate infectivity and treatment responses through exogenous hormone supplementation. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]